• Eukaryotic DNA replication is a conserved mechanism that restricts DNA replication to once per cell cycle. (wikipedia.org)
  • Eukaryotic DNA replication of chromosomal DNA is central for the duplication of a cell and is necessary for the maintenance of the eukaryotic genome. (wikipedia.org)
  • The major enzymatic functions carried out at the replication fork are well conserved from prokaryotes to eukaryotes, but the replication machinery in eukaryotic DNA replication is a much larger complex, coordinating many proteins at the site of replication, forming the replisome. (wikipedia.org)
  • Eukaryotic origins of replication control the formation of several protein complexes that lead to the assembly of two bidirectional DNA replication forks. (wikipedia.org)
  • Maintaining genomic integrity is of utmost importance to eukaryotic cells, which have evolved sophisticated mechanisms to ensure speed, accuracy, and an adequate pool of nucleotide and replication factors as well as high-fidelity repair pathways to correct errors occurring during DNA replication. (bmj.com)
  • Association of the origin recognition complex (ORC) with a replication origin recruits the cell division cycle 6 protein (Cdc6) to form a platform for the loading of the minichromosome maintenance (Mcm 2-7) complex proteins, facilitated by the chromatin licensing and DNA replication factor 1 protein (Cdt1). (wikipedia.org)
  • Each origin is initiated by a combination of regulatory proteins that prepare the chromatin for replication before synthesis (S)-phase entry. (bmj.com)
  • In eukaryotes, the vast majority of DNA synthesis occurs during S phase of the cell cycle, and the entire genome must be unwound and duplicated to form two daughter copies. (wikipedia.org)
  • Then hTopBP1 interacts with ATR-ATRIP through its ATR-activating domain (AD) and stimulates ATR kinase activity [ 8 , 9 ]. (biomedcentral.com)
  • Multiple replicative proteins assemble on and dissociate from these replicative origins to initiate DNA replication. (wikipedia.org)
  • The ORC, Cdc6, and Cdt1 together are required for the stable association of the Mcm2-7 complex with replicative origins during the G1 phase of the cell cycle. (wikipedia.org)
  • Strategies that increase replicative stress while lowering cell cycle checkpoint thresholds may allow unrepaired DNA damage to be inappropriately carried forward in replicating cells, leading to mitotic catastrophe and cell death. (bmj.com)
  • Any obstacles encountered by cells in this process can lead to 'replicative stress' ( Figure 1 ), 1 which may be overcome by replicative stress response proteins, but deficiencies in this response result in accumulated errors in DNA replication and loss of genomic integrity, which lead to cell death. (bmj.com)
  • Thus, hTopBP1 constitutes an important part of the ATR signaling pathway and acts as a molecular bridge that associates the independently recruited 9-1-1 and ATR-ATRIP complexes, thereby leading to checkpoint activation [ 4 ]. (biomedcentral.com)
  • In addition, we investigated several cell cycle-related proteins and found that co-knockdown of hTopBP1 and hMYH significantly diminished cell cycle arrest due to compromised checkpoint kinase 1 (Chk1) activation. (biomedcentral.com)
  • The replisome is responsible for copying the entirety of genomic DNA in each proliferative cell. (wikipedia.org)
  • During ATR signaling in response to DNA damage, Rad17 forms a complex with 9-1-1 and loads onto stalled replication forks [ 4 - 9 ]. (biomedcentral.com)
  • The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast. (academicinfluence.com)
  • Human DNA topoisomerase II-binding protein 1 (hTopBP1) plays an important role in DNA replication and the DNA damage checkpoint pathway. (biomedcentral.com)
  • Our results suggested that hMYH is necessary for the accumulation of hTopBP1 to DNA damage lesion to induce the association of hTopBP1 with 9-1-1 and that the interaction between hMYH and hTopBP1 is essential for Chk1 activation. (biomedcentral.com)
  • Small molecule inhibitors designed to target the DNA damage sensors, such as inhibitors of ataxia telangiectasia-mutated (ATM), ATR, CHK1 and WEE1, impair smooth cell cycle modulation and disrupt efficient DNA repair, or a combination of the above, have demonstrated interesting monotherapy and combinatorial activity, including the potential to reverse drug resistance and have entered developmental pipelines. (bmj.com)
  • In the presence of errors or damage during DNA replication, cell cycle checkpoint nodes and repair machinery work in concert to retard cell cycle progression until sufficient repair has been achieved. (bmj.com)
  • Therefore, we suggest that the interaction between hMYH and hTopBP1 is crucial for activation of the ATR-mediated cell cycle checkpoint. (biomedcentral.com)
  • The pre-RC formation involves the ordered assembly of many replication factors including the origin recognition complex (ORC), Cdc6 protein, Cdt1 protein, and minichromosome maintenance proteins (Mcm2-7). (wikipedia.org)
  • Through its interactions with other proteins via its BRCT domains, hTopBP1 performs diverse functions [ 1 ]. (biomedcentral.com)
  • This kinase has been shown to phosphorylate checkpoint kinase CHK1, checkpoint proteins RAD17, and RAD9, as well as tumor suppressor protein BRCA1. (genetex.com)
  • METHODS/RESULTS: For our study, we had available HCT116 cells (wild-type p53) and HT29 colon tumor cells (mutant p53) and their corresponding CRISPRâ Cas9-generated ATF2-KO clones. (bvsalud.org)
  • The protein encoded by this gene belongs the PI3/PI4-kinase family, and is most closely related to ATM, a protein kinase encoded by the gene mutated in ataxia telangiectasia. (genetex.com)
  • Notably, SCML2 promotes chemoresistance through distinct mechanisms in p53-positive and p53-negative cancer cells. (bvsalud.org)
  • In p53-mutant or p53-negative cancer cells, SCML2 promotes CHK1 and p21 stability by inhibiting their ubiquitination, thereby enhancing the resistance to DNA damage agents. (bvsalud.org)
  • Mutations of this gene are associated with Seckel syndrome. (genetex.com)
  • ATR appears as a good candidate breast cancer susceptibility gene and the current study was designed to screen for ATR germline mutations potentially involved in breast cancer predisposition. (biomedcentral.com)
  • Although no deleterious mutations were identified in the ATR gene, the current study provides an haplotype analysis of the ATR gene polymorphisms, which allowed the identification of a set of SNPs that could be used as tSNPs for large-scale association studies. (biomedcentral.com)
  • We observed that loss of ATF2 triggered dose- and time-dependent 5-FU resistance in HCT116 cells by activating the DNA damage response (DDR) pathway with high p-ATRThr1989 and p-Chk1Ser317 levels accompanied by an increase in the DNA damage marker γ-H2AX in vitro and in vivo using the chicken chorioallantoic membrane (CAM) model. (bvsalud.org)
  • Untreated (-) and treated (+) HCT116 whole cell extracts (30 μg) were separated by 5% SDS-PAGE, and the membrane was blotted with ATR (phospho Thr1989) antibody (GTX128145) diluted at 1:2000. (genetex.com)
  • If most cancer susceptibility is related to fundamental processes of cellular control, rare alleles might turn out to be the more important component and should be detectable by linkage analysis and/or the candidate gene re-sequencing approach [ 5 , 6 ]. (biomedcentral.com)
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
  • Ataxia telangiectasia-mutated and Rad3-related (ATR) is a member of the PIK-related family which plays, along with ATM, a central role in cell-cycle regulation. (biomedcentral.com)
  • ATR (phospho Thr1989) antibody detects ATR (phospho Thr1989) protein at nucleus by immunohistochemical analysis. (genetex.com)
  • ATR (phospho Thr1989) antibody detects ATR (phospho Thr1989) protein at nucleus in human breast carcinoma by immunohistochemical analysis. (genetex.com)
  • ATR (phospho Thr1989) antibody detects ATR (phospho Thr1989) protein at nucleus in human lung by immunohistochemical analysis. (genetex.com)
  • In cultured glioma cells, we show that PAM-OBG is converted to O 6 BG, inhibiting MGMT and sensitizing cells to DNA alkylating agents such as BCNU, CCNU, and Temozolomide (TMZ). (oncotarget.com)
  • In this study, two datasets GSE1009 and GSE142153 were selected to extract expression profile-based data from DN glomerular samples, and 238 differentially expressed genes (DEGs) were screened. (bvsalud.org)
  • CHEK1 was the focus of this study, and the expression level of CHEK1 in glomerular epithelial cell models was verified by qRT-PCR. (bvsalud.org)
  • In a recent study published in Cell, Zhang et al. (bvsalud.org)
  • In contrast to the transcript generated by an alternative splicing site in the intron 41, the one resulting from a deletion of 121 nucleotides in exon 33 is widely expressed, at significant but relatively low levels, in both normal and tumoral cells including normal breast and ovarian tissue. (biomedcentral.com)
  • Gliomas are the most common primary tumors that arise within the brain and have histologic features similar to normal glial cells (i.e., astrocytes, oligodendrocytes, and ependymal cells). (oncotarget.com)